Sequential mTOR inhibitor treatment with temsirolimus in metastatic renal cell carcinoma following failure of VEGF receptor tyrosine kinase inhibitors

2011 ◽  
Vol 31 (4) ◽  
pp. 805-809 ◽  
Author(s):  
Steffen Weikert ◽  
Carsten Kempkensteffen ◽  
Jonas Busch ◽  
Manfred Johannsen ◽  
Viktor Grünwald ◽  
...  
Kidney Cancer ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 151-158
Author(s):  
Katherine Yuxi Tai ◽  
Jad M. El Abiad ◽  
Carol D. Morris ◽  
Mark Christopher Markowski ◽  
Adam S. Levin

BACKGROUND: Checkpoint inhibitors and receptor tyrosine kinase inhibitors (RTKIs) have changed the standard of care for metastatic renal cell carcinoma (mRCC). Anecdotal evidence suggests these therapies may be less effective for treating bone than soft-tissue metastases. PURPOSE: We performed a retrospective review evaluating the relative clinical responses in soft-tissue and bone metastases in patients undergoing therapy using RTKIs and anti-programmed death-1 (PD-1) agents for mRCC. METHODS: Of the 2,212 patients in our institutional cancer registry with renal cell carcinoma (1997–2017), 68 (82 disease courses) were identified with measurable bone and soft-tissue metastases treated with RTKIs and/or PD-1s. Extent of metastasis was quantified at the time of therapy initiation (baseline) and at 3 months, 6 months, and 1 year. Changes in disease status were categorized as complete response, partial response, stable, mixed, or progression of disease according to RECIST v1.1 and MD Anderson criteria. These categories were further organized into “response to treatment” or “evidence of progression” to generate a generalized linear effects model with soft-tissue response as the independent variable and bone response as the dependent variable. Alpha = 0.05. RESULTS: Soft-tissue response correlated with bone response at 3 months (76 disease courses, p = 0.005) and 6 months (48 disease courses, p = 0.017). Of the patients with controlled soft-tissue disease, only 14 (19%) and 15 (32%) had progression in bone at 3 and 6 months, respectively. CONCLUSION: Contrary to anecdotal reports, osseous metastases do not appear to respond worse than soft-tissue metastases to treatment with these agents.


2020 ◽  
Vol 16 (28) ◽  
pp. 2147-2164
Author(s):  
Allen Jacob ◽  
Jaret Shook ◽  
Thomas E Hutson

The VHL mutation– HIF upregulation– VEGF transcription sequence is the principal pathway in the development of renal cell carcinoma. Tyrosine kinase inhibitors target the VEGF receptors to inhibit further growth of renal cell carcinoma tumors. Tivozanib, originally named AV-951 and KRN-951, is a novel, orally bioavailable VEGF tyrosine kinase inhibitor that is selective for VEGF receptors 1, 2 and 3. Further, only picomolar concentrations of tivozanib are required to target these VEGF receptors and prevent phosphorylation; this potency prevents the debilitating side effects that occur with treatments whose mechanisms of action involve broad-spectrum tyrosine kinase inhibition. This review summarizes the growing body of evidence supporting tivozanib's efficacy and safety in the treatment of advanced renal cell carcinoma.


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